Neurons transmit information over long distances by means of a train of action potentials (spikes); while much is known about how the propagating spike (in the axon) is generated, much less is known about how the train originates in the soma and dendrites. While occasional depolarizations of the cell membrane in the somatic region will lead to a spike if they cross threshold (analogous to axons), additional modes of repetitive firing are seen there: the rhythmic firing mode occurs when a prolonged depolarizing current from the synapses (or an experimentally injected current) attempts to keep the membrane potential above threshold. Because of hyperpolarizing spike afterpotentials, this leads to rhythmic firing at a rate proportional to the size of the current; the neuron thus acts as a net-current-to-spike-frequency converter. A third mode is regenerative: a spike may have a depolarizing afterpotential. If large enough, it may rise through the threshold (as it falls following a spike), setting off an extra spike. This extra spike may set off another extra spike, etc. Such a high- frequency burst is an optimal stimulus for downstream cells, but it is merely the consequence of a stimulus which would otherwise elicit only a single spike. This study investigates the origins of all three modes (occasional spike, rhythmic firing, and regenerative firing of repetitive discharge and attempts to relate it to known neuropathophysiology. Disorders of surviving (but malfunctioning) cells, such as in chronic pain, epilepsy, and mental retardation, are usually manifested in abnormal patterns of neuronal discharge rather than silence. Epileptic neurons (best studied of the group) in humans show high-frequency burst firing patterns, strikingly similar to the patterns produced by the regenerative mode in motoneurons. We are examining the threshold and membrane potential behavior during the three modes; we are exploring methods of enhancing and surpressing the regenerative mode; we are regularly comparing our results to those from animals with induced chronic disorders and recordings obtained from humans prior to surgical excision of hyperactive tissue.